Hypertension is a complex disease process involving many pathophysiological changes. In this program project, the individual research topics focus on the theme that cytokines contribute to abnormal blood pressure regulation in angiotensin II-induced hypertension. The strategy of the group is to monitor many relevant variables during the development of hypertension with the goal of defining the complete sequence of events from the introduction of an intervention (angiotensin II or cage switch stress) to the resultant elevation in blood pressure. Among these variables are alterations in neural and endocrine factors, cellular events and molecular and gene characteristics. Five principal investigators from two administrative units have joined to study these changes. Animal models will include mice and rats (experimental hypertension and genetically modified). Among the specific variables measured will be the following: mRNA for specific proteins, enzyme activities, genetic associations, vascular reactivity, blood pressure, hormone levels, endothelium-derived products, cytokines, calcium, reactive oxygen species and arachidonic acid metabolites. Research strategies will utilize the professional expertise and equipment described in two of the core units (Core A, Animal and Core B, Biochemistry). Biostatistical support and scientific management will be coordinated through the Administrative Unit. From these integrated projects, a better understanding of the factors contributing to hypertension will emerge.